In proteomics and other fields of research employing mass spectrometry as an analytical technique, there is increasing demand for high-throughput analysis of large numbers of peptides or other substances in a complex sample. Such analyses are highly beneficial, for example, in connection with biomarker studies that seek to identify differentially expressed proteins between control and diseased samples. Hybrid mass spectrometers, which utilize two or more mass analyzers of different types, have become a popular and valuable tool for quantitative and qualitative analysis of complex biological samples. Hybrid mass spectrometers offer the advantage of joining the capabilities and advantages of different mass analyzer types, thereby avoiding the performance tradeoff associated with use of a single type of mass analyzer. For example, the Orbitrap Elite mass spectrometer, available from Thermo Fisher Scientific, combines the high sensitivity, rapid scan speed and MSn (multiple-stage isolation and dissociation) capability of a two-dimensional quadrupole ion trap mass analyzer with the high resolution/accurate mass performance of an Orbitrap electrostatic trap mass analyzer.
Hybrid mass spectrometers may utilize parallel operation of the different mass analyzers in order to produce more and richer data characterizing the sample. In parallel acquisition techniques, each of the two or more mass analyzers is operated independently and concurrently to perform ion injection, optional ion manipulation (e.g., isolation and fragmentation), and mass spectral acquisition. Parallelized acquisition techniques may be operated in a data-dependent fashion, in which mass spectral data acquired in one of the analyzers is processed in real time to adapt “on the fly” the operation of the mass spectrometer. For example, a commonly employed data-dependent approach involves the selection of precursor ion species for MS/MS or MSn analysis based on the intensities of ion species observed in a full MS spectrum. This approach is sometimes referred to colloquially as “Top N” MS/MS analysis. When implemented in a hybrid mass spectrometer, Top N MS/MS analysis may be conducted by using a first mass analyzer to acquire the full MS spectrum and a second mass analyzer to perform MS/MS analysis of selected precursor ion species. In this manner, the acquisition of a full MS spectrum for identification of high-intensity ions may be performed concurrently with MS/MS analysis of precursor ion species identified in a previously acquired MS spectrum.
While the use of hybrid mass spectrometers, parallel mass analyzer operation and data-dependent analysis has provided significant gains in performance, the ability to rapidly and efficiently analyze complex samples is limited by the design and available modes of operation of prior art mass spectrometer systems. Typically, hybrid mass spectrometers utilize mass analyzers of different types (e.g., an electrostatic mass analyzer and an ion trap mass analyzer) having different analysis cycle times (i.e., the time required to fill the mass analyzer to a target population, to cool the ions and perform any desired manipulations, and to separate and detect the ions to generate a mass spectrum). The mismatch between analysis cycle times may result in “dead time”, wherein one of the mass analyzers remains inactive until the completion of an analysis cycle by the other mass analyzer. Inefficient utilization of mass analyzers may be exacerbated by mass spectrometer architectures that do not allow one of the mass analyzers to be filled until the other has completed a mass spectral scan.
Against this background, there is a need in the art for instrument designs and modes of operation that provide enhanced efficiency of mass analyzer utilization and the capacity for greater high-throughput analysis, particularly of complex biological samples.